Investigation of patients with neurological dysfunction. The general aim of this project is to obtain a more precise understanding of the multiple factors possibly related, either singly or in combination, to the pathogenesis of neurological disorders. Focus is currently placed on multiple sclerosis (MS). Patients with sporadic disease, patients with a family history of demyelinating disease, as well as identical and nonidentical twins who are either concordant or discordant for the disease are being evaluated. The studies include assessment of immunogenetic background, cellular immune reactivity to a number of viruses and cell surface molecules on leukocytes in the blood. The reactivity and production of immunoglobulins in the cerebrospinal fluid are being measured by highly sensitive techniques. These investigations have recently been extended to tropical spastic paraparesis (TSP) associated with HTLV-I. Magnetic resonance imaging is being used to assess the extent and magnitude of lesions in MS and TSP. A phase III cooperative trial of cyclosporine A in chronic-progressive MS is currently in progress. During this trial clinical status, findings by magnetic reasonance imaging and immune status are being followed.